Publications by authors named "Maroua Jalouli"

15 Publications

  • Page 1 of 1

The relationship of 3'UTR HLA-G14-bp insertion/deletion and +3142 C/G polymorphisms and soluble HLA-G expression with gynecological cancers: An updated meta-analysis.

Immun Inflamm Dis 2022 07;10(7):e645

Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Objectives: Human leukocyte antigen-G (HLA-G) is implicated in several cancers and is considered to be an immune checkpoint regulator. We determined the association between polymorphisms in the 3' untranslated region of HLA-G and soluble HLA-G (sHLA-G) expression with gynecological cancers (GCs).

Methods: A meta-analysis was conducted to examine the association between HLA-G14-bp insertion (I)/deletion (D) and +3142C/G polymorphism in GC and to evaluate sHLA-G expression RESULTS: We revealed a significant association between the +3142C/G polymorphism and invasive cervical cancer (ICC) based on the allelic model G versus C (odds ratio [OR] = 0.738, 95% confidence interval [CI] = 0.563-0.966, p = 0.027), dominant GG+GC versus CC (OR = 0.584, 95% CI = 0.395-0.862, p = 0.007), and codominant GG versus CC (OR = 0.527, 95% CI = 0.312-0.891, p = 0.017) models, suggesting that the G allele and GG genotype are protective against ICC. In gynecological precancerous patients with human papillomavirus (HPV) infection, we found that the 14-bp I/D under the codominant DD versus DI model (OR = 0.492, 95% CI = 0.241-1.004, p = 0.051) was of borderline significance. Soluble HLA-G levels were significantly higher in patients compared with healthy controls (standardized mean differences [SMD] = 1.434, 95% CI = 0.442-2.526, p = 0.005). Stratification by cancer type revealed that the sHLA-G levels were significantly increased in cervical cancer (SMD = 4.889, 95% CI = 0.468-9.310, p = 0.030) and in subjects of Asian ethnicity (SMD = 4.889, 95% CI = 0.467-9.309, p = 0.030).

Conclusions: HLA-G14-bp I/D and +3142 C/G polymorphisms are associated with GC and HPV-associated cervical cancer. In addition, we found significantly increased sHLA-G levels in cancer patients. These results provide a basis for further studies in diagnostics and immunotherapy of GC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iid3.645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168547PMC
July 2022

3'UTR-HLA-G polymorphisms and circulating sHLA-G are associated with breast cancer: Evidence from a meta-analysis.

Immunol Lett 2022 Aug 22;248:78-89. Epub 2022 Jun 22.

Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia. Electronic address:

Background: Human leukocyte antigen-G (HLA-G) gene polymorphisms and circulating sHLA-G have often been linked to the risk of breast cancer (BC). However, the results remain controversial. To resolve this issue, we performed a meta-analysis of HLA-G gene polymorphisms and sHLA-G levels in BC.

Methods: We performed a meta-analysis on the association of HLA-G 14-bp Insertion/Deletion (Ins/Del) and HLA-G +3142 C/G polymorphisms with BC as well as the relationship between sHLA-G and the disease outcome.

Results: Pooled analysis showed a statistically significant association between the HLA-G 14-bp Ins/Del polymorphism and BC susceptibility for the overall population and for Caucasians. The Del allele and genotypes with at least one copy of the Del allele presented significant risks for BC. For HLA-G +3142 C/G polymorphism, the G allele significantly decreased the risk of BC for the overall population and for Caucasians, indicating that the G allele was a protective factor against BC and that the C allele was a significant risk factor for BC. The meta-analysis revealed a significantly increased level of sHLA-G patients with BC compared to the control group for the overall population, Caucasians and Asians.

Conclusion: The present meta-analysis showed a major association of both HLA-G 14-bp Ins/Del and +3142 C/G polymorphisms with BC susceptibility, suggesting Del and C variants as highly significant risk factors for BC. The present study also showed significantly higher sHLA-G levels in patients with BC compared to healthy controls. Our pooled results suggested a critical role of HLA-G in BC, thereby providing evidence to use HLA-G as a biomarker and a therapeutic tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2022.06.010DOI Listing
August 2022

Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries.

Int J Mol Sci 2022 Jun 7;23(12). Epub 2022 Jun 7.

Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23126397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224321PMC
June 2022

Benzene exposure causes structural and functional damage in rat ovaries: occurrence of apoptosis and autophagy.

Environ Sci Pollut Res Int 2022 Jun 6. Epub 2022 Jun 6.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Studies to date have provided evidence for damage that can occur from hydrocarbon benzene on different tissues/organs. However, little is known regarding the possible influence of this hydrocarbon on female reproduction. In this study, female Wistar rats were treated with low (2000 ppm), middle (4000 ppm), and high (8000 ppm) doses of benzene by inhalation for 30 min daily for 28 days. Benzene exposure adversely affected ovarian function and structure by inducing histopathological changes and altering reproductive steroid hormone release. In addition, benzene-exposed ovaries exhibited increased TMR red fluorescent signals at middle and high doses, revealing significant apoptosis. Interestingly, the investigation of the autophagic protein marker LC3 showed that this protein significantly increased in all benzene-treated ovaries, indicating the occurrence of autophagy. Moreover, ovaries from benzene-treated groups exhibited differential regulation of several specific genes involved in ovarian folliculogenesis and steroidogenesis, including the INSL3, CCND1, IGF-1, CYP17a, LHR, ATG5, and GDF9 genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-022-21289-5DOI Listing
June 2022

Ethylbenzene exposure disrupts ovarian function in Wistar rats via altering folliculogenesis and steroidogenesis-related markers and activating autophagy and apoptosis.

Ecotoxicol Environ Saf 2022 Jan 14;229:113081. Epub 2021 Dec 14.

King Saud University, Department of Zoology, College of Science, Saudi Arabia.

Ethylbenzene is a hydrocarbon that is extensively used in both industry and in the home and has been reported as toxic to various tissues. Nevertheless, its effect on ovarian function remains unclear. For this purpose, we assessed ovarian tissue morphology, evaluated protein and gene expression related to folliculogenesis and steroidogenesis, and investigated the involvement of both apoptosis and autophagy processes in this effect. Female Wistar albinos rats were treated with 2000, 4000 and 8000 ppm doses of ethylbenzene by inhalation for 30 min daily for one month. Ovaries were then removed and proceeded for histopathological and molecular analyses. We found that ethylbenzene affected folliculogenesis by decreasing the number of growing follicles and increasing the number of abnormal follicles, leading to faster female reproductive aging. Interestingly, it disrupted female reproductive hormone balance, including progesterone, estradiol, testosterone and IGF-1 plasma levels. The latter protein, along with GDF-9, significantly decreased in all ethylbenzene-treated groups, leading to the disruption of follicular cell proliferation and development. TUNEL assay study showed that ethylbenzene exposure significantly increased the number of apoptotic cells. The mRNA levels of genes involved in granulosa cell proliferation and differentiation, such as INSL3, CCND2 and ACTB, were significantly decreased. In addition, LC3 protein expression increased, and its encoding gene was upregulated, suggesting that ethylbenzene treatment induced autophagy. In summary, ethylbenzene exposure caused structural and functional disorders of the ovary by disrupting the normal growth of follicles, altering reproductive hormone balance, inhibiting the expression of key reproductive proteins and triggering autophagy as well as apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.113081DOI Listing
January 2022

Personalization of medical treatments in oncology: time for rethinking the disease concept to improve individual outcomes.

EPMA J 2021 Dec 7;12(4):545-558. Epub 2021 Oct 7.

Department of Zoology, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia.

The agenda of pharmacology discovery in the field of personalized oncology was dictated by the search of molecular targets assumed to deterministically drive tumor development. In this perspective, genes play a fundamental "causal" role while cells simply act as causal proxies, i.e., an intermediate between the molecular input and the organismal output. However, the ceaseless genomic change occurring across time within the same primary and metastatic tumor has broken the hope of a personalized treatment based only upon genomic fingerprint. Indeed, current models are unable in capturing the unfathomable complexity behind the outbreak of a disease, as they discard the contribution of non-genetic factors, environment constraints, and the interplay among different tiers of organization. Herein, we posit that a comprehensive personalized model should view at the disease as a "historical" process, in which different spatially and timely distributed factors interact with each other across multiple levels of organization, which collectively interact with a dynamic gene-expression pattern. Given that a disease is a dynamic, non-linear process - and not a static-stable condition - treatments should be tailored according to the "timing-frame" of each condition. This approach can help in detecting those critical transitions through which the system can access different attractors leading ultimately to diverse outcomes - from a pre-disease state to an overt illness or, alternatively, to recovery. Identification of such tipping points can substantiate the predictive and the preventive ambition of the Predictive, Preventive and Personalized Medicine (PPPM/3PM). However, an unusual effort is required to conjugate multi-omics approaches, data collection, and network analysis reconstruction (eventually involving innovative Artificial Intelligent tools) to recognize the critical phases and the relevant targets, which could help in patient stratification and therapy personalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13167-021-00254-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495186PMC
December 2021

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer's Disease.

Curr Neuropharmacol 2022 ;20(1):126-146

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah,Saudi Arabia | Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can, in turn, induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1570159X19666210826130210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9199559PMC
January 2022

Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates.

Bioorg Chem 2021 09 8;114:105071. Epub 2021 Jun 8.

University of Monastir, Faculty of Science of Monastir, Laboratory of Heterocyclic, Chemistry, Natural Products and Reactivity, TeamMedicinal Chemistry and Natural, Products (LR11ES39), Department of Chemistry, Avenue of Environment, 5019 Monastir, Tunisia. Electronic address:

Two series of 3,5-disubstituted isoxazoles (6a-e) and 1,4-disubstituted triazoles (8a-e) derivatives have been synthesized from tyrosol (1), a natural phenolic compound, detected in several natural sources such as olive oil, and well-known by its wide spectrum of biological activities. Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between tyrosol-alkyne derivative 2 and two series of aryl nitrile oxides (5a-e) and azides (7a-e) regiospecifically afforded 3,5-disubstituted isoxazoles (6a-e) and 1,4-triazole derivatives (8a-e), respectively in quantitative yields. Synthesized compounds were purified and characterized by spectroscopic means including 1D and 2D NMR techniques and HRMS analysis. The newly prepared hybrid molecules have been evaluated for their anticancer and hemolytic activities. Results showed that most derivatives displayed significant antiproliferative activity against human glioblastoma cancer cells (U87) in a dose-dependent manner. Compounds 6d (IC = 15.2 ± 1.0 μg/mL) and 8e (IC = 21.0 ± 0.9 μg/mL) exhibited more potent anticancer activity. Moreover, most derivatives displayed low hemolytic activity, even at higher concentrations which suggested that these classes of compounds are suitable candidates for further in vivo investigations. The obtained results allow us to consider the newly synthesized isoxazole- and triazole-linked tyrosol derivatives as promising scaffolds for the development of effective anticancer agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2021.105071DOI Listing
September 2021

The flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl, as a potential therapeutic agent for breast cancer with a promoting effect on ovarian function.

Phytother Res 2021 Nov 28;35(11):6170-6180. Epub 2021 Apr 28.

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

It is widely known that breast cancer cells eventually develop resistance to hormonal drugs and chemotherapies, which often compromise fertility. This study aimed to investigate the effect of the flavonoid, kaempferol-3-O-apiofuranosyl-7-O-rhamnopyranosyl (KARP), on 1) the viability of MCF-7 breast cancer cells and 2) ovarian function in rats. A dose-dependent decrease in MCF-7 cell survival was observed, and the IC50 value was found to be 48 μg/ml. Cells in the control group or those exposed to increasing concentrations of KARP experienced a similar generation of reactive oxygen species and induction of apoptosis. For the rats, estradiol levels correlated negatively to KARP dosages, although a recovery was obtained at administration of 30 mg/kg per day. Noteworthily, when compared against the control, this dosage led to significant increases in mRNA levels for CYP19, CYP17a, CCND2, GDF9, and INSL3 among the treatment groups, and ER1 and ER2 mRNA levels decreased in a dose-dependent manner. KARP shows great promise as an ideal therapy for breast cancer patients since it induced apoptosis and autophagy in cancerous cells without harming fertility in our animal model. Future investigations on humans are necessary to substantiate these findings and determine its efficacy as a general line of treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.7067DOI Listing
November 2021

Fucoidan supplementation modulates hepato-renal oxidative stress and DNA damage induced by aflatoxin B1 intoxication in rats.

Sci Total Environ 2021 May 30;768:144781. Epub 2020 Dec 30.

Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030 Besançon Cedex, France.

Aflatoxins are a common food contaminant of global concern. Aflatoxin B (AFB) intoxication is associated with serious health hazards. Recently, fucoidan (FUC) has gained much attention from pharmaceutical industry due to its promising therapeutic effects. The impacts of FUC on AFB-induced liver and kidney injures have not been sufficiently addressed. This research was conducted to evaluate the ameliorative effect of FUC in AFB1-induced hepatorenal toxicity model in rats over 14 days. Five groups were assigned; control, FUC (200 mg/kg/day, orally), AFB (50 μg/kg, i.p.), and AFB plus a low or high dose of FUC. AFB induced marked hepatorenal injury elucidated by substantial alterations in biochemical tests and histological pictures. The oxidative distress instigated by AFB enhanced production of malondialdehyde (MDA) and nitric oxide (NO) along with reduction in the reduced-glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. DNA damage in the liver and kidney tissues has been demonstrated by overexpression of proliferating cell nuclear antigen (PCNA). Unambiguously, FUC consumption alleviates the AFB-induced mitochondrial dysfunction, oxidative harm, and apoptosis. These ameliorated effects are proposed to be attributed to fucoidan's antioxidant and anti-apoptotic activities. Our results recommend FUC supplementation to food because it exerts both preventive and therapeutic effects against AFB-induced toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.144781DOI Listing
May 2021

Genetic Diversity of SARS-CoV2 and Environmental Settings: Possible Association with Neurological Disorders.

Mol Neurobiol 2021 May 6;58(5):1917-1931. Epub 2021 Jan 6.

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

The new coronavirus (CoV), called novel coronavirus disease 2019 (COVID-19), belongs to the Coronaviridae family which was originated from the sea market in Wuhan city in China, at the end of the year 2019. COVID-19 and severe acute respiratory syndrome (SARS) are belonging to the same family (Coronaviridae). The current outbreak of COVID-19 creates public concern and threats all over the world and now it spreads out to more than 250 countries and territories. The researchers and scientists from all over the world are trying to find out the therapeutic strategies to abate the morbidity and mortality rate of the COVID-19 pandemic. The replication, spreading, and severity of SARS-CoV2 depend on environmental settings. Noteworthy, meteorological parameters are considered as crucial factors that affect respiratory infectious disorders, although the controversial effect of the meteorological parameter is exposed against COVID-19. Besides, COVID-19 accelerates the pathogenesis of the neurological disorders. However, the pathogenic mechanisms between COVID-19 and neurological disorders are still unclear. Hence, this review is focused on the genomics and ecology of SARS-CoV2 and elucidated the effects of climatic factors on the progression of COVID-19. This review also critically finds out the vulnerability between COVID-19 and neurological disorders based on the latest research data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-020-02239-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786338PMC
May 2021

Selective HIF-1 Regulation under Nonhypoxic Conditions by the p42/p44 MAP Kinase Inhibitor PD184161.

Mol Pharmacol 2017 11 16;92(5):510-518. Epub 2017 Aug 16.

Centre de recherche du CHU de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Québec, Canada

Hypoxia-inducible factor-1 (HIF-1) is a key gene regulator for cellular adaptation to low oxygen. In addition to hypoxia, several nonhypoxic stimuli, including hormones and growth factors, are essential for cell-specific HIF-1 regulation. Our studies have highlighted angiotensin II (AngII), a vasoactive hormone, as a potent HIF-1 activator in vascular smooth muscle cells (VSMC). AngII increases HIF-1 transcriptional activity by modulating specific signaling pathways. In VSMC, p42/p44 mitogen-activated protein kinase (MAPK) pathway activation is essential for HIF-1-mediated transcription during AngII treatment. The present study shows that PD184161, a potent MEK1/2 inhibitor, is an HIF-1 blocker in Ang II-treated VSMC. Unlike PD98059, a widely-used MEK1/2 inhibitor, we found that PD184161 blocked AngII-driven HIF-1 protein induction in a dose-dependent manner. Interestingly, the effect of PD184161 was specific to nonhypoxic activators, since HIF-1 induction by hypoxia (1% O) was unaffected under similar conditions. VSMC treatment with MG132, a proteasome inhibitor, indicated that PD184161 influenced HIF-1 protein stability. PD184161 also increased HIF-1 binding to von Hippel-Lindau tumor suppressor protein, an E3 ligase component and an indication of HIF-1 hydroxylation. Finally, we show that PD184161 blocked mitochondrial ROS (mtROS) production and cellular ATP levels, at the same time enhancing ascorbate availability in AngII-treated VSMC. Taken together, our study indicates that, independently of p42/p44 MAPK activation, PD184161 blocks mtROS generation by AngII, leading to re-establishment of cellular ascorbate levels, increased VHL binding, and decreased HIF-1 stability. Therefore, this study reveals a previously unsuspected role for PD184161 as an HIF-1 inhibitor in VSMC under nonhypoxic conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/mol.117.108654DOI Listing
November 2017

Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women.

Onco Targets Ther 2017 24;10:1207-1216. Epub 2017 Feb 24.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S112165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338938PMC
February 2017

The prolyl isomerase Pin1 regulates hypoxia-inducible transcription factor (HIF) activity.

Cell Signal 2014 Aug 12;26(8):1649-56. Epub 2014 Apr 12.

Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC G1R 3S3, Canada. Electronic address:

Hypoxia-inducible transcription factor-1 (HIF-1) plays a decisive role in cell survival and adaptation to hypoxic stress by controlling the expression of genes involved in oxygen homeostasis. HIF-1 activity is fine-tuned through specific post-translational modifications of its essential HIF-1α subunit. Among these modifications, phosphorylation is important for HIF-1 transcriptional activity. Studies have shown that the mitogen-activated protein kinases, p42/p44 MAPKs, directly phosphorylate HIF-1α and increase HIF-1-mediated transcription. Pin1, a peptidyl-prolyl cis/trans isomerase, targets a number of proteins containing a phosphorylated Ser/Thr-Pro motif. Pin1 isomerization causes a change in target protein conformation which can modify their activity. Here, we identify Pin1 as an important HIF-1α partner. Immunoprecipitation and pull-down studies show that Pin1 interacts with HIF-1α. We demonstrate that the interaction between Pin1 and HIF-1α is regulated through p42/p44 MAPK pathway activation. By performing proteolysis studies, our results indicate that Pin1 catalytic activity generates a conformational change in HIF-1α. Finally, our work shows that Pin1 is required for gene-specific HIF-1 transcriptional activity. Our results indicate that the prolyl isomerase Pin1 regulates HIF-1 transcriptional activity by interacting with HIF-1α and promoting conformational changes in a p42/p44 MAPK phosphorylation-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2014.04.005DOI Listing
August 2014

Transitin is required for the differentiation of avian QM7 myoblasts into myotubes.

Dev Dyn 2010 Nov;239(11):3038-47

Centre de recherche PROTEO et Département de biologie moléculaire, biochimie médicale et pathologie, Université Laval, Québec (Qc), Canada.

Transitin is a nestin-like intermediate filament protein co-expressed with vimentin in the precursor cells of the myogenic and neurogenic lineages of the avian embryo. To understand its role in myogenesis, stable cell lines expressing transitin-targeted siRNAs were derived from the quail muscle cell line QM7. When cells were cultured in differentiation medium, we found that transitin knockdown prevented myoblast fusion and myotube formation. MyoD mRNA could be detected in transitin siRNA-transfected cells, but upregulation of myogenin and desmin expression was impaired compared to control cells. In addition, transitin siRNA cells maintain high levels of Pax7 expression suggesting that QM7 myoblasts into which transitin expression has been attenuated display a muscle progenitor cell phenotype (Pax7(+)/MyoD(+)/myogenin(-)/desmin(-)). These observations indicate that transitin plays an important role in the initiation of the myogenic program in avian muscle progenitor cells in acting downstream of MyoD and upstream of myogenin during the lineage progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dvdy.22448DOI Listing
November 2010
-->